A DNA methylation signature discriminates between excellent and non-response to lithium in patients with bipolar disorder type 1.
Sci Rep
; 10(1): 12239, 2020 07 22.
Article
in En
| MEDLINE
| ID: mdl-32699220
ABSTRACT
Lithium (Li) is the cornerstone maintenance treatment for bipolar disorders (BD), but response rates are highly variable. To date, no clinical or biological marker is available to reliably define eligibility criteria for a maintenance treatment with Li. We examined whether the prophylactic response to Li (assessed retrospectively) is associated with distinct blood DNA methylation profiles. Bisulfite-treated total blood DNA samples from individuals with BD type 1 (15 excellent-responders (LiERs) versus 11 non-responders (LiNRs)) were used for targeted enrichment of CpG rich genomic regions followed by high-resolution next-generation sequencing to identify differentially methylated regions (DMRs). After controlling for potential confounders we identified 111 DMRs that significantly differ between LiERs and LiNRs with a significant enrichment in neuronal cell components. Logistic regression and receiver operating curves identified a combination of 7 DMRs with a good discriminatory power for response to Li (Area Under the Curve 0.806). Annotated genes associated with these DMRs include Eukaryotic Translation Initiation Factor 2B Subunit Epsilon (EIF2B5), Von Willebrand Factor A Domain Containing 5B2 (VWA5B2), Ral GTPase Activating Protein Catalytic Alpha Subunit 1 (RALGAPA1). Although preliminary and deserving replication, these results suggest that biomarkers of response to Li may be identified through peripheral epigenetic measures.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bipolar Disorder
/
DNA Methylation
/
Lithium
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Sci Rep
Year:
2020
Document type:
Article
Affiliation country:
Francia